Brit. J. Ophthal. (1965) 49, 359

MALIGNANT MELANOMA OF THE ORBIT IN A CASEOF OCULODERMAL MELANOSIS*

(NAEVUS OF OTA)BY

BARRIE JAYDepartment ofPathology, Institute of Ophthalmology, University ofLondon

APART from the value of recording a further example of a rare disease, it is hoped thatthis case of a malignant melanoma of the orbit occurring in a patient with oculo-dermal melanosis will shed some light upon certain aspects of melanotic lesions.

Case ReportA 64-year-old woman was admitted to the Newcastle upon Tyne General Hospital (under the careof Mr. Fenton Braithwaite) with a one year's history of progressive protrusion of her righteye. She had pigmentation of the skin of her right lower lid and temporal region, melanosis bulbi,and unilateral proptosis resulting in restriction of ocular movements. The right orbit was decom-pressed and a biopsy of orbital tissue showed fat and fibrous tissue only. She was re-admitted tohospital six months later with a recurrence of the right proptosis and a soft tumour was felt in theright temporal region, the lateral wall of the orbit having been removed at the previous operation.In view of these findings the right orbital contents were removed en bloc with the temporalis muscleand the pigmented area of temporal skin. Ten months later the patient died from congestivecardiac failure and multiple secondary deposits of melanoma. It is not known whether a post-mortem examination was performed.

Pathological FindingsMacroscopic Examination.-The specimen consisted of the right orbital contents

and eyelids, together with a large flap of temporal skin and underlying temporalismuscle. A partially pigmented retro-ocular tumour was present, closely applied tothe posterior pole of the eye and located mainly above the optic nerve. Severalpoorly defined areas of pigmentation were present beneath the bulbar and palpebralconjunctiva and a few oval pigmented lesions were present in the substance of thelower lid.

Microscopic Examination.-The specimen showed the pathological features of twodistinct, though probably related, conditions:

(1) Malignant melanoma of the orbit. The retro-ocular tumour was found to be alightly pigmented malignant melanoma composed predominantly of anaplastic

* Received for publication January 6, 1965.359

epithelioid cells lying in a well-marked reticulin framework. Areas of necrosis andhaemorrhage were present in the tumour which was partly enclosed in a fibrouscapsule (Figs I and 2).

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*t'.>*'.y"-"'"'r'¢XS a~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~FIG. 1.-Malignant melanoma of the orbitcontaining areas of necrosis and haemorrhage.H.& E. x 90.

FIG. 2.-High-power view of tumour cellsshown in Fig. 1. x 415.

(2) Oculodermal melanosis. There was marked melanosis of the whole uveal tractresulting from an increased number of apparently normal fusiform melanocytes inthis tissue (Fig. 3). Similar cells were present along the intra-scleral channels (Fig. 4)and in the optic nerve-head, but there was no evidence of an intra-ocular tumour.Scattered fusiform melanocytes were present in the dermis of the eyelids (Figs 5 and 6)and temporal skin. These cells lay parallel to the surface of the skin and did notdisrupt its architecture. Similar cells were present in the orbicularis and temporalismuscles and in the orbital tissue. Small circumscribed heavily pigmented tumours

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........FIG. 3. Melanosis of the choroidresulting from an increased number offusiform melanocytes in this tissue(the retina separated from the choroidduring fixation and is not present in thisfield). H. & E. x 90.

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inrscea cha nel. H. E. x 9 .. ..<. .'<'' .g;

BARRIE JA Y360

MALIGNANT MELANOMA WITH OCULODERMAL MELANOSIS

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FIG. 5.-Dermal melanosis of the eyelid.Melanocytes lying parallel to the surface ofthe skin are present debp in the dermis and donot disrupt its architecture. H. & E. x 90.

were present in the substance of the eye-lids (Fig. 7); they were composed ofdensely packed fusiform cells of benignappearance similar to the scattered cellspresent elsewhere in the specimen.

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FIG. 6.-High-power view of melanocytesshown in Fig. 5. x415.

FIG. 7.-Blue naevus of eyelid composed ofheavily pigmented fusiform melanocytes.H.& E. x 90.

DiscussionBesides developing a malignant melanoma of the orbit, this patient had a wide-

spread disturbance of melanin pigmentation involving the tissues over the distribu-tion of the ophthalmic and maxillary divisions of the trigeminal nerve. This wide-spread melanotic lesion consisted of spindle-shaped melanocytes situated in the skin,orbicularis muscle, conjunctiva, sclera, uveal tract, and orbital tissue, these melano-cytes being identical in appearance with those that occur in Mongolian spots and bluenaevi. In Mongolian spots and dermal melanoses the aberrant melanocytes aresparsely scattered in the dermis, while in blue naevi they are present in greaternumbers, forming a tumour and disrupting the normal architecture of the skin. Theassociation of melanosis bulbi with a dermal melanosis over the distribution of thetrigeminal nerve is known eponymously as the naevus of Ota, or naevus fusco-caeruleus ophthalmo-maxillaris (Ota, 1939). The first description of this conditionwas that by Hulke (1861) and since then there have been scattered reports of similarcases in the literature (Mishima and Mevorah, 1961). Lund and Kraus (1962) con-sidered the naevus of Ota to be a dermal melanosis rather than a tumour, while Ito

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(1952) believed it to be a form of blue naevus. Dorsey and Montgomery (1954)described the naevus of Ota as essentially a Mongolian spot located on the side of theface and involving the eye, its histology varying between that of a Mongolian spotand that of a cellular blue naevus. It seems probable that melanosis bulbi and thenaevus of Ota are different degrees of severity of the same abnormality, and in orderto emphasize both the occasional association between dermal melanosis and melano-sis bulbi, and the relationship they bear to each other, it is suggested that the term"oculodermal melanosis" (Lund and Kraus, 1962) be applied to the naevus of Ota.The histological appearance of the present case supports the view of Dorsey andMontgomery (1954), for it is essentially a dermal melanosis with small scattered bluenaevi in the eyelids.Tanino (1939) described 26 cases of oculodermal melanosis and classified them

into five types:(1) Mild orbital type. Faint pigmented spots scattered over the upper and lower

eyelids and in the skin over the temple.(2) Mild zygomatic type. Pigmentation in the skin between the sulcus infra-

palpebralis and sulcus nasolabialis.(3) Moderate type. Pigmentation in the skin of the eyelids, zygomatic region,

cheek, and temple.(4) Intensive type. The pigmentation extends further, involving the scalp,

forehead, and brow.(5) Bilateral type.In Tanino's (1939) series the eye was involved in 17 cases. In the series of cases

reported by Ito (1952), 65 were present at birth and 41 appeared after birth. Thiscondition of oculodermal melanosis, which is most frequently seen in oriental races,has been reported in Caucasians (Dorsey and Montgomery, 1954) and in Negroes(Mishima and Mevorah, 1961).

In order to explain the occurrence of aberrant melanocytes in tissues over thedistribution of the trigeminal nerve it is necessary to postulate either that the ultimatedistribution of these pigment-producing cells is determined by the presence of nerves,or that these cells arise from constituents of the nerves. There is considerableexperimental evidence that melanoblasts migrate from the neural crest in embryo anddifferentiate into melanocytes when they reach their destination in skin, mucousmembrane, uveal tract, and leptomeninges. This has been shown to be true foramphibia, birds, and mammals (Rawles, 1947), although experimental confirmationfor its occurrence in man is still lacking. There is evidence, however, that in the firsthalf of human foetal development melanoblasts are present in a fairly definite layerin the dermis, and that by the eleventh or twelfth week of foetal life they have startedto penetrate the epidermis (Zimmermann and Becker, 1959). Mongolian spots anddermal melanoses represent postnatal remnants of this general pigmentary layer inthe dermis, a layer which occurs normally in the dermis of adult apes (Adachi, 1903).In the present case the occurrence of melanocytes along the intrascleral channels isevidence of their close association with intrascleral nerves, and as both melanoblastsand Schwann cells are derived from the neural crest, these cells may arise fromcommon precursors which differentiate when they reach their destination, or theymay arise separately yet reach their destination by the same pathway.

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MALIGNANT MELANOMA WITH OCULODERMAL MELANOSIS

Although it is generally agreed that dermal melanocytes originate from the neuralcrest and are atavistic remnants of the dermal pigmentary layer, no one has yetanswered the question posed by Dorsey and Montgomery (1954) as to why, if bluenaevus cells and ordinary naevus cells are of the same origin, the ordinary naevuscells do not show dendritic processes-like the blue naevus cells-when they dropdown from the epidermis into the dermis. It is possible that the tumour-formingpotentialities of melanocytes, once they have reached the basal layer of the epidermis,are affected by their proximity to epithelial cells, and this would also account for therarity of malignant blue naevi as compared with malignant melanomata of the skin.

Malignant change has not been reported in a Mongolian spot or in a case of dermalmelanosis, and in only three cases has a malignant melanoma arisen in oculodermalmelanosis. In two of these cases (Dorsey and Montgomery, 1954) the malignantmelanomata were considered to have arisen from subcutaneous blue naevi, while in athird case (Hulke, 1861) a malignant melanoma of the choroid developed. In contrastto this rare occurrence of malignant change in oculodermal melanosis, malignantmelanomata of the uveal tract develop in cases of melanosis bulbi more frequentlythan can be expected by chance (Duke-Elder, 1938).The association of two rare conditions, malignant melanoma of the orbit and

oculodermal melanosis, as in the present case, is unlikely to occur by chance and,since oculodermal melanosis may present only faint pigmentation of the skin, onewonders whether it has been missed in previously reported cases of primary malignantmelanoma of the orbit. This association of melanosis bulbi with dermal melanosisalso suggests that these two conditions may have a similar aetiology, and if this is thecase a "naevus" of the uveal tract could be equated to a blue naevus of the skin, and amalignant melanoma of the uveal tract to a malignant blue naevus of the skin. Thisview is supported by Ashton (1964), who stated that naevus cells have never beenconclusively demonstrated in the uveal tract, nor could they be expected to occur atthis site, for they are a strain of cells arising from epidermal melanocytes.

SummaryA case is presented of a malignant melanoma of the orbit arising in association

with oculodermal melanosis. The rare association of melanosis bulbi with dermalmelanosis suggests that these two conditions have a similar aetiology and theimplications of this hypothesis are discussed.

I should like to thank Mr. Fenton Braithwaite for permission to publish the clinical details of this case,and Professor Norman Ashton for his unfailing encouragement and advice.

REFERENCESADACHI, B. (1903). Z. Morph. Anthrop., 6, 1.ASHTON, N. (1964). Brit. J. Ophthal., 48, 650.DORSEY, C. S., and MONTGOMERY, H. (1954). J. invest. Derm., 22, 225.DUKE-ELDER, W. S. (1938). "Text-book of Ophthalmology", vol. 2, p. 1395. Kimpton, London.HULKE, J. W. (1861). Ophthal. Hosp. Rep., 3, 279.ITO, M. (1952). Tohoku J. exp. Med., 55, suppl. 1, p. 21.LUND, H. Z., and KRAUS, J. M. (1962). "Atlas of Tumor Pathology", sect. 1, fasc. 3: Melanotic Tumors of

the Skin, p. 25. Armed Forces Institute of Pathology, Washington.MISHIMA, Y., and MEVORAH, B. (1961). J. invest. Derm., 36, 133.OTA, M. (1939). Jap. J. Derm., 46, 99.RAWLES, M. E. (1947). Physiol. Zool., 20, 248.TANINO, H. (1939). Jap. J. Derm., 46, 107.ZIMMERMANN, A. A., and BECKER, S. W. Jr. (1959). In "Pigment Cell Biology", ed. M. Gordon, p. 159.

Academic Press, New York.

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